The abuse of phenethylamine and tryptamine based hallucinogenic drugs continues to be a serious problem that is now rivaled by the appearance of numerous cannabinoid agonists and cathinones (bath salts). Data from the DEA has show the appearance of novel hallucinogenic phenethylamines and tryptamines either previously encountered in insignificant amounts or not seen at all. This is due in part to the publication of cookbook chemical syntheses and detailed accounts of the doses used and hallucinogenic effects seen in humans for almost all of the 179 phenethylamine and 53 tryptamine analogs that were synthesized and self-administered by A. T. Shulgin and his associates during more than 30 years. This information has been widely disseminated via the Internet. These are disturbing developments that substantially aid and encourage clandestine drug production and may presage a resurgence in phenethylamine and tryptamine abuse and exacerbating the overall problems of hallucinogenic drug abuse. We have begun a program to synthesize and evaluate a number of these hallucinogenic agents and their antagonists. We recently studied racemic 3,4-methylenedioxypyrovalerone in drug discrimination, thermoregulation, and locomotor activity paradigms in comparison with methamphetamine (METH) and methylenedioxymethamphetamine (MDMA). Our studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA. In another study, we examined the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) as a hallucinogen. This drug has been reported to produce LSD effects by HIV patients and non-infected teens who smoke the crushed tablets. Efavirenz failed to maintain responding in rats that self-administer cocaine, and it failed to produce a conditioned place preference. Although efavirenz interacts with a number of sites, we showed that the dominant behavioral profile in a number of paradigms was consistent with LSD-like interaction with the 5-HT2A receptor and that this profile was absent in 5-HT2A-knockout mice.